Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: To assess the efficacy of belimumab in patients with SLE who had high disease activity at baseline, as defined by SELENA-SLEDAI score ≥10.
Methods: In 2 randomized, double-blind, multicenter phase 3 studies, 1684 SLE patients with SELENA-SLEDAI ≥6 at baseline were treated with placebo, or belimumab 1 or 10 mg/kg, plus standard SLE therapy (NCT00071487/NCT00583362). In a post-hoc analysis, the SLE Responder Index (SRI) at wk 52, flares, corticosteroid use, fatigue, and the SF-36 vitality domain were examined in a subgroup of patients with baseline SELENA-SLEDAI ≥10.
Results: 877 patients (52%) had SELENA-SLEDAI scores ≥10 on entry to the BLISS trials: 299, 283, and 296 were randomized to placebo, and belimumab 1 and 10 mg/kg, respectively. Mean baseline characteristics were similar across treatment groups. In patients with SELENA-SLEDAI ≥10 vs ≤9, >80% vs 56% were anti-double-stranded−DNA positive and 55%/67% vs 34%/55% had low C3/C4 levels. In patients with SELENA-SLEDAI ≥10 vs all patients in the BLISS trials, 89% vs 57% had >3 organ systems involved. Belimumab 1 and 10 mg/kg significantly improved SRI response, and reduced prednisone use in high disease activity patients at wk 52 (see table). Treatment with belimumab 10 mg/kg generally resulted in a greater response than with 1 mg/kg and placebo regarding reduction in severe flare risk, and improvements in SRI response, fatigue, and SF-36 vitality at wk 52.
Conclusion: Belimumab 10 mg/kg significantly reduced disease activity, flares, corticosteroid use, and fatigue in SLE patients with high disease activity, as defined by baseline SELENA-SLEDAI scores ≥10.
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Efficacy in Patients With SELENA-SLEDAI Scores ≥10 at Baseline |
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Response parametera |
Placebo (n = 299) |
Belimumab |
|
|
1 mg/kg (n = 283) |
10 mg/kg (n = 296) |
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SRI response: wk 52, % p value |
44.1 |
58.0 <0.001 |
63.2 <0.001 |
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No new BILAG A and ≤1 new B score p value |
65.4 |
73.5 0.024 |
74.3 0.017 |
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≥4-point reduction in SELENA-SLEDAI p value |
48.0 |
60.4 0.001 |
66.2 <0.001 |
|
No worsening in PGA p value |
63.1 |
73.1 0.006 |
74.0 0.004 |
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Patients with ≥1 severe flare, % Severe flare risk over 52 wk: HR (95% CI)b p value |
28.8 |
21.6 0.73 (0.52−1.01) 0.054 |
18.2 0.59 (0.42−0.83) 0.003 |
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Prednisone reduction ≥25% from baseline to ≤7.5mg/day: wk 40−52, n (%)c p value |
12/181 (6.6) |
32/182(17.6) 0.002 |
31/186(16.7) 0.004 |
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% patients with reduction in baseline prednisone from > 7.5 to ≤7.5 mg/d at week 52 p value |
16/181 (8.8) |
35/182(19.2) 0.007 |
41/186 (22.0) <0.001 |
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Mean FACIT-Fatigue score improvement: wk 52 p value |
3.38 |
4.76 0.103 |
5.12 0.024 |
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Mean SF-36 vitality score change p value |
7.82 |
9.69 0.196 |
10.76 0.044 |
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ap values represent comparisons of belimumab treatment with placebo; bCox proportional hazards model; cincludes only patients with baseline prednisone >7.5 mg/d. BILAG, British Isles Lupus Assessment Group; FACIT, Functional Assessment of Chronic Illness Therapy; PGA, Physician’s Global Assessment. |
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Disclosure:
A. E. Clarke,
GSK,
2,
HGS, BMS, MedImmune,
5,
GSK,
8;
S. Manzi,
SEE ATTACHED,
2,
SEE ATTACHED,
5,
SEE ATTACHED,
7;
M. Petri,
HGS, GSK,
5;
R. Furie,
HGS, GSK,
2,
HGS, GSK,
5,
HGS, GSK,
8;
R. F. van Vollenhoven,
Abbott, BMS, GSK, HGS, MSD, Pfizer, Roche, UCB,
2,
Abbott, BMS, GSK, HGS, MSD, Pfizer, Roche, UCB,
5;
S. Cooper,
Human Genome Sciences, Inc.,
1,
Human Genome Sciences, Inc.,
3;
Z. J. Zhong,
HGS,
1,
HGS,
3;
W. W. Freimuth,
HGS,
1,
HGS,
3;
A. Weinstein,
HGS, Genentech, Savient, Pfizer,
2,
HGS, GSK, Pfizer,
5,
HGS, GSK,
8.
ACR Meeting Abstracts - https://acrabstracts.org/abstract/efficacy-of-belimumab-in-systemic-lupus-erythematosus-patients-with-high-baseline-disease-activity/